Small study suggests gene therapy may slow Alzheimer's

Results from a preliminary six-person study of gene therapy for Alzheimer's disease hint the treatment may delay decline, Mark H. Tuszynski, M.D., Ph.D., and colleagues report in the April 24 online edition of Nature Medicine.

Nearly two years after treatment, participants declined more slowly than before their surgery and at less than the average expected rate. In addition, imaging with positron emission tomography (PET) showed increased brain activity in treated individuals as compared with untreated individuals with Alzheimer's disease.

The therapy involves genetically engineering some of a person's own skin cells to produce nerve growth factor, a chemical important in survival and repair of the brain's nerve cells. Researchers then inject these engineered cells into several brain regions severely affected by Alzheimer's disease. In theory, nerve growth factor produced by the implants will improve function and slow decline of the other cells, delaying Alzheimer progression.

"These results need to be interpreted with cautious optimism because the study is so small," says William H. Thies, Ph.D., Alzheimer's Association vice president, Medical and Scientific Affairs. "The course of Alzheimer's disease varies tremendously, and with only six individuals it's really impossible to tell whether the benefit was due to the treatment or natural fluctuation in symptoms. Another limitation is there was no control group receiving a placebo."

"If the benefit is borne out in a larger trial, though, it may revive interest in other strategies for getting nerve growth factors into the brain. There are drugs that can stimulate the brain's own production of these factors, but development stalled out after mixed results from early clinical trials. Proof-of-concept through gene therapy could renew interest in those pharmaceutical approaches."

The chief purpose of this small study was to assess the treatment's safety rather than its effectiveness. The project started out with eight participants, but complications prevented the first two therapy recipients from completing the study. Those two people, who were sedated but not given general anesthesia, moved unexpectedly while the procedure was in progress, leading to cerebral bleeding and, in one case, death. The remaining six participants received anesthesia and did not experience any serious side effects. Another small trial of the procedure is under way at Rush University Medical Center in Chicago.

Dr. Tuszynski, a neurologist at the University of California at San Diego (UCSD), received Alzheimer's Association research grants in 1999 and 2003 for work related to this study. Co-author Leon Thal, M.D., director of UCSD's Alzheimer's Disease Center, also received Association funding in 2000 for related work.

Alzheimer's Association funding of these investigators:

Mark H. Tuszynski, M.D., Ph.D.University of CaliforniaSan Diego, CaliforniaDelivering Neurotrophic Factors into the CNS by Gene Therapy1999 Investigator-Initiated Research Grant — $180,000 over three years